Sympathetic neuroblasts undergo a developmental switch in trophic dependence

Sympathetic neurons require NGF for survival, but it is not known when these cells first become dependent on neurotrophic factors. We have examined in vitro mitotically active sympathetic neuroblasts immuno-isolated from different embryonic stages, and have correlated this functional data with the expression of neurotrophin receptor mRNAs in vivo. Cells from E14.5 ganglia are supported by neurotrophin-3 (NT-3) in a serum-free medium, but not by NGF; NT-3 acts as a bona fide survival factor for these cells and not simply as a mitogen. By birth, sympathetic neurons are well-supported by NGF, whereas NT-3 supports survival only weakly and at very high doses. This change in neurotrophin-responsiveness is correlated with a reciprocal switch in the expression of trkC and trkA mRNAs by sympathetic neuroblasts in vivo. These data suggest that neurotrophic factors may control neuronal number at earlier stages of development than previously anticipated. They also suggest that the acquisition of NGF-dependence may occur, at least in part, through the loss of receptors for these interim survival factors.